Orthogonal ion sampling for apci mass spectrometry

ABSTRACT

A method and apparatus are disclosed wherein a plurality of electric fields and of orthogonal spray configurations of vaporized analyte are so combined as to enhance the efficiency of analyte detection and mass analysis. The invention provides reduced noise and increased signal sensitivity in both API electrospray and APCI operating modes.

INTRODUCTION

[0001] This application is a continuation of U.S. patent applicationSer. No. 09/910,222, which is a continuation of U.S. patent applicationSer. No. 09/204,213, now U.S. Pat. No. 6,294,779, which is acontinuation of 09/030,676 filed Feb. 25, 1998, now U.S. Pat. No.6,278,110, which in turn is a continuation of U.S. patent applicationSer. No. 08/794,248 filed Feb. 3, 1997, now U.S. Pat. No. 5,750,988,which in turn is a continuation of U.S. patent application Ser. No.08/555,250, now abandoned, which in turn is a continuation-in-part ofU.S. patent application Ser. No. 08/273,250, filed Jul. 11, 1994, nowU.S. Pat. No. 5,495,108, issued Feb. 27, 1996.

[0002] The invention relates to a method and apparatus for obtainingimproved signal relative to noise without loss of ion collectionefficiency for use in mass spectrometry, including LC/MS (liquidchromatography/mass spectrometry), especially as regards the techniqueof generating analyte ions known as Atmospheric Pressure ChemicalIonization (APCI).

BACKGROUND

[0003] Liquid chromatography and mass spectrometry have proven powerfulanalytical tools in identifying molecular components of our world.Liquid chromatography is a fundamental separation technique. Massspectrometry is a means of identifying “separated” components accordingto their characteristic “weight” or mass-to-charge ratio. The liquideffluent from LC is prepared for ionization and analysis using any of anumber of techniques. A common technique, electrospray, involvesspraying the sample into fine droplets.

[0004] Early systems for electrospray LC/MS utilized flow splitters thatdivided the HPLC (high performance liquid chromatography) columneffluent. As a result of the effluent splitting, only a small portion,typically 5-50 micro liters per minute, was introduced into the “spraychamber”. The bulk of the column effluent did not enter the spraychamber but went directly to a waste or fraction collector. Becauseelectrospray/mass spectrometry (ES/MS) generally provides aconcentration sensitive detector, it was not necessary to analyze theentire column effluent flow to obtain sensitive results. Resultsobtained by splitting are comparable in sensitivity to those obtained byintroduction of the entire column effluent flow into the spray chamber(assuming equal charging and sampling efficiencies).

[0005] Such low flow rates enabled generation of an electrosprayedaerosol solely through the manipulation of electrostatic forces.However, the use of flow splitters gained a bad reputation due topotential plugging problems and poor reproducibility.

[0006] Newer electrospray systems generate a charged or ionized aerosolthrough the combination of electrostatic forces and some form ofassisted nebulization. Nebulization is the process of breaking a streamof liquid into fine droplets. Nebulization may be “assisted” by a numberof means, including but not limited to pneumatic, ultrasonic or thermalassists. The assisted nebulization generates an aerosol from the HPLCcolumn effluent, while electric fields induce a charge on the aerosoldroplets. The charged aerosol undergoes an ion evaporation processwhereby desolvated analyte ions are produced. Ideally, only thedesolvated ions enter the mass spectrometer for analysis.

[0007] A challenge in any assisted nebulizer system, is designing thevacuum system leading to the mass spectrometer such that desolvated ionsenter, but relatively large solvated droplets present in theelectrosprayed aerosol are prevented from entering. Several designapproaches arc currently in use, but none has solved all the challenges.None of the assisted nebulization methods currently practiced providereliable sensitivity along with robust instrumentation.

[0008] In conventional electrospray/nebulization mass spectrometrysystems, the electrosprayed aerosol exiting from the nebulizer issprayed directly towards the sampling orifice or other entry into thevacuum system. That is, the electrosprayed aerosol exiting from thenebulizer and entry into the vacuum system are located along a commoncentral axis, with the nebulizer effluent pointing directly at the entryinto the vacuum system and with the nebulizer being considered to belocated at an angle of zero (0) degrees relative to the common centralaxis.

[0009] One previous approach directed at improving performance adjuststhe aerosol to spray “off-axis”. That is, the aerosol is sprayed“off-axis” at an angle of as much as 45 degrees with respect to thecentral axis of the sampling orifice. In addition, a counter current gasis passed around the sampling orifice to blow the solvated droplets awayfrom the orifice. The gas velocities typically used generate a plume ofsmall droplets. Optimal performance appears to be limited to a flow rateof 200 microliters per minute or lower.

[0010] In another system, an aerosol is generated pneumatically andaimed directly at the entrance of a heated capillary tube; the heatedcapillary exits into the vacuum system. Instead of desolvated ionsentering the capillary, large charged droplets are drawn into thecapillary and the droplets are desolvated while in transit. Theevaporation process takes place in the capillary as well. Exiting thecapillary in a supersonic jet of vapor, the analyte ions aresubsequently focused, mass analyzed and detected.

[0011] This system has several disadvantages and limitations, includingsample degradation, re-clustering, and loss of sensitivity. Sensitivesamples are degraded due to the heat. In the supersonic jet expansionexiting the capillary, the desolvated ions and vapor may recondense,resulting in solvent clusters and background signals. While theseclusters may be re-dissociated by collisionally induced processes, thismay interfere in identification of structural characteristics of theanalyte samples. The large amount of solvent vapor, ions and dropletsexiting the capillary require that the detector be arrangedsubstantially off-axis with respect to the capillary to avoid noise dueto neutral droplets striking the detector. Removing the large volume ofsolvent entering the vacuum system requires higher capacity pumps.

[0012] Still another system generates the electrosprayed aerosolultrasonically, uses a counter current drying gas, and most typicallyoperates with the electrosprayed aerosol directed at the samplingcapillary. Several serious disadvantages plague this configuration. Theoptimal performance is effectively limited to less than five hundred(500) microliters per minute. Adequate handling of the aqueous mobilephase is problematic. Furthermore, the apparatus is complex and prone tomechanical and electronic failures.

[0013] In another commonly used system, a pneumatic nebulizer is used atsubstantially higher inlet pressures (as compared with other systems).This results in a highly collimated and directed electrosprayed aerosol.This aerosol is aimed off axis to the side of the orifice and at thenozzle cap. Although this works competitively, there is still some noisewhich is probably due to stray droplets. The aerosol exiting thenebulizer has to be aimed carefully to minimize noise while maintainingsignal intensity; repeated and tedious adjustments are often required.

[0014] While the techniques are varied with respect to the type ofnebulization assist, techniques can be broadly characterized along thelines of what process is used for accomplishing ionization of theanalyte. Atmospheric Pressure Ionization—Electrospray (API-ES or ESherein) and Atmospheric Pressure Chemical Ionization (APCI) differ inthe ionization mechanism. Each technique is suited to complementaryclasses of molecular species.

[0015] The techniques are, in practice, complementary owing to differentstrengths and weaknesses. Briefly, APT-ES is generally concentrationdependent (that is to say, higher concentration equals betterperformance), and performs well in the analysis of moderately to highlypolar molecules. It works well for large, biological molecules andpharmaceuticals, especially molecules that ionize in solution andexhibit multiple charging. API-ES also performs well for smallmolecules, provided the molecule is fairly polar. Low flow rates enhanceperformance. APCI, on the other hand, performs with less dependence onconcentration and performs better on smaller non-polar to moderatelypolar molecules. Higher flow rates enhance performance.

[0016] At the most fundamental level, APCI involves the conversion ofthe mobile phase and analyte from the liquid to the gas phase and thenthe ionization of the mobile phase and analyte molecules. APCI is a softionization technique that yields charged molecular ions and adduct ions.APCI, as implemented in the hardware described herein, actually includesseveral distinct ionization processes, with the relative influence ofeach process dependent on the chemistry of the mobile phase and theanalyte. What is desired is an assisted nebulization LC/MS configurationfor APCI that operates in a complementary range of flow rates as doesAPI-ES. What is further needed and wanted from the practitioner's pointof view is a mass spectrometry apparatus easily and interchangeablyconfigurable for operation in either API-ES or APCI mode with increasedsensitivity in both operating modalities. What is further desired isrobust instrumentation that provides sensitive results without constantcalibrating or other process interruptive maintenance procedures.

SUMMARY OF INVENTION

[0017] In one embodiment the invention relates to an apparatus forconverting a liquid solute sample into vaporized and ionized moleculescomprising:

[0018] a first passageway having a center axis, an orifice for acceptinga liquid solute sample, an interior chamber within which the liquidsolute sample is converted into vaporized molecules, and an exit fordischarging the vaporized molecules;

[0019] a charged point voltage source having the point arranged adjacentto the first passageway exit which ionizes the vaporized molecules intoionized molecules;

[0020] an electrically conductive housing connected to a second voltagesource and having an opening arranged adjacent to the first passagewayexit wherein the ionized molecules formed by the point charge voltagesource are interposed between the point charge voltage source and thehousing;

[0021] a second passageway arranged within the housing adjacent to theopening and connected to a third voltage source, the second passagewayhaving a center axis, an orifice for receiving ionized molecules and anexit, wherein the center axis of the second passageway is arranged intransverse relation to the center axis of the first passageway such thatthe ionized molecules move laterally through the opening in the housingand thereafter pass into the second passageway under the influence ofelectrostatic attraction forces generated by the second and thirdvoltage sources.

[0022] In another embodiment the invention relates to an apparatus forconverting a solute sample into ionized molecules, comprising:

[0023] a first passageway having a center axis, an orifice for acceptinga solute sample, an interior chamber within which the solute sample isvaporized, and an exit for discharging the vaporized molecules;

[0024] a charged-point voltage source having the point arranged adjacentto the first passageway exit for ionizing the vaporized molecules;

[0025] a second passageway connected to a voltage source and arranged adistance from the exit of the first passageway, the second passagewayhaving an entrance having a center axis, an orifice for receiving theionized molecules from the first passageway, and an exit, wherein thecenter axis of the second passageway is arranged in transverse relationto the center axis of the first passageway such that the ionizedmolecules move laterally into the orifice of the second passageway underthe influence of electrostatic attraction forces generated by anelectric field; and

[0026] a housing adjacent to the second passageway wherein a voltagesource is connected to the housing.

[0027] In another embodiment the invention relates to an apparatus forconverting a liquid solute sample into ionized molecules, comprising:

[0028] (a) a first passage way having a center axis and an exit;

[0029] (b) a charged-point voltage source arranged adjacent to said exitof the first passageway;

[0030] (c) a second passageway having a center axis;

[0031] (d) a housing adjacent to the second passageway wherein a voltagesource is connected to the housing;

[0032] (e) at least one additional voltage source connected to at leastone of the passageways;

[0033] wherein the first passageway is capable of converting the liquidsolute sample into vaporized molecules;

[0034] wherein the charged-point voltage source is capable of convertingthe vaporized molecules into ionized molecules;

[0035] wherein the additional voltage source results in a difference inpotential thereby creating an electric field sufficient to move ionizedmolecules into the second passageway; and

[0036] wherein the center axis of the first passageway is positionedtransverse to the center axis of the second passageway at an angle offrom about 75 degrees to about 105 degrees.

[0037] In another embodiment the invention relates to an apparatus forconverting a solute ample into ionized molecules, comprising:

[0038] a first passageway having a center axis, an orifice for acceptinga solute sample, an interior chamber within which the solute sample isvaporized, and an exit for discharging the vaporized molecules,

[0039] a charged-point voltage source having the point arranged adjacentto the first passageway exit for ionizing the vaporized molecules;

[0040] a second passageway arranged a distance from the exit of thefirst passageway, the second passageway having an entrance having acenter axis, an orifice for receiving the ionized molecules from thefirst passageway, and an exit, wherein the center axis of the secondpassageway is arranged in transverse relation to the center axis of thefirst passageway such that the ionized molecules move laterally into theorifice of the second passageway under the influence of electrostaticattraction forces generated by an electric field; and

[0041] an electrically conductive element connected to a voltage source,wherein the element is arranged adjacent to the exit of the firstpassageway and wherein vaporized molecules exiting the first passagewayis interposed between the element and the entrance of the secondpassageway.

[0042] The invention provides the capability of ionizing effluent fromconventional high performance liquid chromatography (HPLC) at flow ratesof greater than one (1) ml/minute without flow splitting. The inventionprovides that ionization may be accomplished in a variety of manners,including atmospheric pressure chemical ionization (APCI) as well asatmospheric pressure ionization electrospray (API-ES).

[0043] As applied to API-ES, the invention further provides thatdesolvated ions be separated from comparatively large volumes ofvaporized aerosol from the column effluent, and then, while keeping outas much of the aerosol as possible, introducing the desolvated ions intothe vacuum system for mass detection and analysis. The inventionprovides the capability of separating desolvated ions from the largevolumes of vapor and directing the desolvated ions from the ionizationchamber (typically operating at atmospheric pressure) to the massspectrometer (MS) (operating at 10⁻⁶ to 10⁻⁴ torr). The inventiveseparation capability preserves instrument sensitivity because themaximum amount of analyte (in the form of desolvated ions) is introducedinto vacuum system to be mass analyzed and detected. Furthermore, theinventive sensitivity is preserved without overwhelming the vacuumsystem with large volumes of liquid droplets or vapor.

[0044] Orthogonal ion sampling according to the present invention allowsmore efficient enrichment of the analyte by spraying the chargeddroplets in the electrosprayed aerosol past a sampling orifice, whiledirecting the solvent vapor and solvated droplets in the electrosprayedaerosol away from the ion sampling orifice such that they do not enterthe vacuum system.

[0045] As applied to APCI, the invention further provides that ions beseparated from comparatively large volumes of vaporized column effluent,and then, while keeping out as much of the vapor as possible,introducing the ions into the vacuum system for mass detection andanalysis. The invention provides the capability of separating desolvatedions from the large volumes of vapor and directing the desolvated ionsfrom the ionization chamber (typically operating at atmosphericpressure) to the mass spectrometer (MS) (operating at 10⁻⁶ to 10⁻⁴torr). The inventive separation capability preserves instrumentsensitivity because the maximum amount of analyte (in the form of ions)is introduced into the vacuum system to be mass analyzed and detected,but incomplete solvent-to-vapor phase change in the heater does notappear as noise, in contrast to the situation with the straight-onconfigurations of the prior art. Furthermore, the inventive sensitivityis preserved without overwhelming the vacuum system with large volumesof liquid droplets or vapor and residual liquid-phase solvent.

[0046] The noise level in an apparatus configured according to thepresent invention is reduced by as much as five fold over currentsystems, resulting in increased signal relative to noise, and henceachieving greater sensitivity. Performance is simplified and the systemis more robust because optimization of the position of the firstpassageway, gas flow and voltages show less sensitivity to smallchanges. The simplified performance and reduced need for optimizationalso result in a system less dependent upon flow rate and mobile phaseconditions. The reduced need for optimization extends to changing mobilephase flow rates and proportions. Practically speaking, this means thatan apparatus configured to employ the inventive system can be run undera variety of conditions without adjustment.

BRIEF DESCRIPTION OF THE DRAWINGS

[0047]FIG. 1 is a representation of an API-ES apparatus according to thepresent invention.

[0048]FIG. 2 is a representation of an alternate embodiment of an API-ESapparatus according to the present invention.

[0049]FIG. 3 is a representation of an alternate embodiment of an API-ESapparatus according to the present invention.

[0050]FIG. 4 is a representation of an alternate embodiment of an API-ESapparatus according to the present invention.

[0051]FIG. 5 is a representation of an APCI embodiment according to thepresent invention.

DETAILED DESCRIPTION OF THE INVENTION

[0052]FIG. 1 depicts an apparatus 10 configured according to the currentinvention. As in conventional sample introduction, a liquid sample isconducted through a nebulizer and into a first passageway 14, exitingvia a second orifice 15 (the exit of the first passageway 14) underconditions which create a vapor of charged droplets or electrosprayedaerosol 11. The invention provides a rather different electrosprayparticle transport as compared with conventional electrospray processes.FIG. 1 depicts the transport of the electrospray droplets from the exit15 of the first passageway 14, through the distance to the opening ororifice 17 of a second passageway 22, and entering the second passageway22 where the orientation angle θ of the center axis of the exitingelectrosprayed aerosol 11 and the center axis of the second passageway22 is between 75 and 105 degrees with respect to each other. The anglemay be greater than 105 and, in principle, as great as 180 degrees; inpractice, best results have been obtained at settings at or near 90degrees. (As shown in FIG. 1, the angle θ defines the location of thefirst passageway 14, that is, the nebulizer or other source ofelectrosprayed aerosol 11, relative to the second passageway 22, thatis, the entry into the vacuum system. The angle θ is considered to bezero (0) degrees when the exit 15 for the electrosprayed aerosol 11 andthe center axis of the first passageway 14 are pointing directly at theentrance 17 and the center axis of the second passageway 22. The angle θis considered to be 180 degrees when the exit 15 for the electrosprayedaerosol 11 and the center axis of the first passageway 14 are pointingdirectly away from the entrance 17 and the center axis of the secondpassageway 22.)

[0053] The charged droplets forming the electrosprayed aerosol areelectrostatically attracted laterally across a gap between the exit 15of the first passageway 14 into the opening 17 of the second passageway22. The electrostatic attraction is generated by attaching voltagesources to components of the apparatus. A first voltage source (notshown) is connected to a housing 16 which houses the second passageway22. The housing 16 is not necessarily an enclosure but may be any shapethat can act as a guide for the ions and can support fluid dynamics of adrying gas (discussed below). A second voltage source (not shown) isconnected to the second passageway 22. The first passageway 14 isgenerally kept at ground potential.

[0054] In the course of crossing the gap and approaching the opening 17to the second passageway 22, especially after passing through an opening21 in the housing 16 containing the second passageway 22, ti eelectrosprayed aerosol is subjected to the cross flow of a gas 20—acondition that operates to remove solvent from the droplets, therebyleaving charged particles or ions. The ions are amenable to analysis byoperation of an analytic instrument capable of detecting and measuringmass and charge of particles such as a mass spectrometer (not shown).The second passageway 22 exits into the mass spectrometer or equivalentinstrument.

[0055] A standard electrospray MS system (HP 5989) with a pneumaticnebulizer provides the base structure. A spray box 12 of plexiglass orsome other suitable material for preventing shock and containing noxiousvapors replaces the standard spray chamber. Within the spray box 12, thenebulizer and first passageway 14 may be arranged in a variety ofconfigurations, so long as the distances between the separate highvoltage sources are sufficient to prevent discharges. Additionalsurfaces at high voltage may be used to shape the electrical fieldsexperienced by the electrosprayed aerosol. In the embodiment depicted inFIG. 1, the system includes a drying gas 20 to aid desolvation andprevent droplets in the electrosprayed aerosol 11 from entering theorifice 17 of the second passageway 22 and the vacuum system (notshown). An alternate embodiment could include a heated capillary as thesecond passageway 22 in an internal source off-axis geometry, such thatthe capillary is off-axis with respect to quadrupole and detectorcomponents.

[0056] The positive ion configuration shown in FIG. 1 typically has thesecond voltage source set approximately at −4.5 kV, the first voltagesource at −4 kV, and the first passageway 14 (wherein the passageway iscomprised of a needle) set at relative ground. Gas, usually nitrogen atnominally 200 to 400 degrees Centigrade and approximately ten standardliters per minute, is typically used as a cross flow drying gas,although other gases can be used. The drying gas 20 flows across theaperture at approximately 90 degrees to the axis of the chargedmolecule; in the electrosprayed aerosol.

[0057] The term “passageway”, as used herein with respect to the secondpassageway, means “ion guide” in any form whatsoever. It is possiblethat the passageway is of such short length relative to the openingdiameter that it may be called an orifice. Other ion guides, includingcapillaries, which are or may come to be used, can operate in theinvention. The configuration; herein are not meant to be restrictive,and those skilled in the art will see possible configurations notspecifically mentioned here but which are included in the teaching andclaims of this invention.

[0058]FIG. 5 illustrates the inventive apparatus as embodying andconfigured for APCI.

[0059] As can readily be observed by even a quick perusal of the FIG. 1and FIG. 5 set side by side, the invention provides that embodiments forAPI-ES and APCI share much of the same hardware. It is apparent to oneof average skill in the art that the configurations depicted herein, aswell as many suggested by the illustrative examples, can be adoptedinterchangeably with relatively straightforward modification ofinput/output interfaces. FIG. 5 references elements common to FIG. 1through use of the same numerical identification. By way of background,classical APCI is a multi step process involving the steps of

[0060] 1) nebulization of the mobile phase and analyte (breaking intodroplets);

[0061] 2) vaporization of the droplets;

[0062] 3) ionization of the mobile phase molecules by electrons from thecharge source generating a corona discharge;

[0063] 4) ionization of the analyte molecules by the mobile phase ions.

[0064]FIG. 5 depicts an apparatus 100 configured according to thecurrent invention. The sample is nebulized (not shown) by any of numberof known nebulization methods, and the resultant droplets proceed intoand through a vaporization chamber 110. The vaporization chamber 110 isformed by a capillary or other tube-like structure 120 composed of glassor ceramic or other suitable material. The tube-like structure 120 issubjected to controlled heating through close association with a heatingdevice 130. In the preferred embodiment, both the tube-like structure120 and the heating device 130 are of a length of several or moreinches, the length being determined by the extent to which the heatingdevice 130 is effectively insulated and, being insulated, howeffectively the conditions in the vaporization chamber interior 135promote ionization of the solvent molecules.

[0065] The vaporization chamber exit 140 allows the vaporized solventand analyte in the aerosol to pass into an intervening space or gap 145.The molecules typically form a corona (not depicted) at this stage.Because the vaporization chamber is typically at ground potential, theexiting molecules “see” a relatively large charge (either negative orpositive) from a charge source 150. The charge source 150 is a chargedpoint (a needle) in the preferred embodiment and the charge source ispositioned so as to optimally induce charge transfer among the moleculescollected in the gap 145. At this point, APCI takes place. The chargedpoint creates a corona discharge in the ambient nitrogen atmosphere. Thehot jet of gas from exit (140), composed of solvent molecules andanalyte molecules, enters the corona discharge region, wherein some ofthe molecules are ionized. Ionization processes include electron impactionization and charge transfer reactions (also called chemicalionization). The ions are attracted toward the second passageway due tothe electric fields created by the voltages applied to variouscomponents of the system. In the embodiment shown, the analyte ions areelectrostatically attracted to a complementary (either positive ornegative) charge from a voltage source (not shown) applied to thehousing 16 of a second passageway 22 which leads to the mass analyzer(not shown) and a stronger relative charge from a voltage source (notshown) applied to the second passageway 22 itself, thereby attractingthe analyte ions into the second passageway 22 through the opening 17thereto.

[0066] The orientation angle θ defining the location of the vaporizationchamber exit 140 relative to the second passageway 22 is between 75 and105 degrees. The angle may be greater that 105 degrees; in principle, itmay be as great as 180 degrees. However, best results have been obtainedat angles at or near 90 degrees. (As shown in FIG. 5, the angle θ, whichdefines the location f the vaporization chamber exit 140, is measuredwith respect to the center axis defined by the second passageway 22,that is, the entry into the vacuum system. The angle θ is considered tobe zero (0) degrees when the vaporization chamber exit 140 and thecenter axis of the vaporization chamber 110 are pointing directly at theentrance 17 and the center axis of the second passageway 22. The angle θis considered to be 180 degrees when the vaporization chamber exit 140and the center axis of the vaporization chamber 110 are pointingdirectly away from the entrance 17 and the center axis of the secondpassageway 22.) The vaporization chamber 110 is generally kept at groundpotential.

[0067] In the preferred embodiment, an HP G 1075A APCI accessoryaccomplishes nebulization as mobile phase and analyte are sprayed out ofa small needle. The concentric flow of nebulizing gas tears the streamof liquid into fine droplets in the aerosol. A heated tube in the APCIAccessory vaporizes the droplets of mobile phase and analyte as thedroplets pass through the tube. The temperature of the tube isadjustable relative to the volatility of the mobile phase (lowvolatility indicates need for higher temperature). The selectedtemperature must substantially complete vaporization without thermallydegrading the analyte.

[0068] After being vaporized, the mobile phase molecules ionize andsubsequently react with and ionize the analyte molecules. The analyteions thus produced are subject to the separation and direction affordedby the orthospray invention as taught herein.

EXAMPLES

[0069] A number of different configurations have been proven possible.Examples of certain tested configurations follow.

[0070]FIG. 2 shows a configuration of the invention in which a thirdvoltage source, a plate 24, is positioned beside the exit 15 of thefirst passageway 14 and distal to the side near to which the firstvoltage source, the opening 21 in the housing 16, and the opening 17 tothe second passageway 22 are positioned. The plate 24 runs a positivevoltage relative to the charge on the housing 16. Experiments show theelectrosprayed aerosol “isees” a mean voltage between the plate 24 andthe charged housing 16. Results suggest that the repeller effect may becaptured and ion collection yield increased by careful sculpting of boththe electric field and the gas flow patterns.

[0071]FIG. 3 shows a two voltage source system as in FIG. 2 with theaddition of a grounded spray chamber 26. The spray chamber 26 operatesto contain the electrosprayed aerosol and route condensed vapor towaste.

[0072]FIG. 4 shows the addition of a ring-shaped electrode 28 encirclingthe electrosprayed aerosol exiting from the needle or first passageway14 at ground, with all of the elements configured as in FIG. 3. Thering-shaped electrode 28 induces a charge in the droplets by virtue ofthe potential difference in charge between the droplets and thering-shaped electrode 28. Other potentials in the system can be used todirect the sampling of ions.

[0073]FIG. 5 illustrates APCI embodiment of the invention taught herein.The typical relative voltages are: source 150 set at between 1.2 kV and2 kV; the surface of the housing 16 immediately adjacent to the entranceto the second passageway 22 set at approximately 3.5 kV; and the secondpassageway 22 set at a slightly greater charge of about 4 kV (both thesurface of the housing 16 and the second passageway 22 oppositelycharged from charge of the source 150). The delta voltage ranges frombetween about 4 to 6 kV.

What is claimed is:
 1. A method of providing ionized analyte moleculesto a mass spectrometer, comprising: vaporizing a fluid mixture of mobilephase molecules and analyte molecules as the mixture travels to an exithaving an axis; ionizing the analyte molecules with a corona dischargein a vicinity of the exit; and directing the ionized analyte moleculesat an angle of between about 75 and about 105 degrees with respect tothe exit axis toward a passageway into the mass spectrometer.
 2. Themethod of claim 1, wherein the ionized analyte molecules are directed atan angle of about 90 degrees.
 3. The method of claim 1, furthercomprising: desolvating mobile phase molecules from the ionized analytemolecules.
 4. The method of claim 1, further comprising: generating apotential gradient in a region between the exit and the passageway intothe mass spectrometer.
 5. The method of claim 4, wherein the directingof the ionized analyte molecules comprises attracting the ionizedanalyte molecules toward the passageway into the mass spectrometer byaction of the potential gradient.
 6. A method of providing ionizedanalyte molecules to a mass spectrometer, comprising: nebulizing a fluidmixture of mobile phase molecules and analyte molecules into an aerosol;ionizing the analyte and mobile phase molecules in the aerosol; sprayingthe aerosol through an exit having an axis; exposing the sprayed aerosolto a potential gradient generated by an electrode having a potentialdifference with respect to the exit; and directing the ionized analytemolecules in the aerosol at an angle of between about 75 and about 105degrees with respect to the exit axis toward a passageway into the massspectrometer and away from the electrode by action of the potentialgradient.
 7. The method of claim 6, wherein the ionized analytemolecules are directed at an angle of about 90 degrees.
 8. The method ofclaim 6, further comprising: desolvating mobile phase molecules from theionized analyte molecules.
 9. The method of claim 8, wherein the mobilephase molecules are desolvated by subjecting the ionized analytemolecules to a drying gas as they are directed toward the passagewayinto the mass spectrometer.
 10. A method of providing ionized analytemolecules to a mass spectrometer, comprising: nebulizing a fluid mixtureof mobile phase molecules and analyte molecules into an aerosol;spraying the aerosol through an exit having an axis; ionizing theanalyte and mobile phase molecules in the aerosol by passing the aerosolthrough an annular electrode adjacent to the exit; and directing theionized analyte molecules in the aerosol at an angle of between 75 and105 degrees with respect to the exit axis toward a passageway into themass spectrometer.
 11. The method of claim 10, wherein the ionizedanalyte molecules are directed at an angle of about 90 degrees.
 12. Themethod of claim 10, further comprising: desolvating mobile phasemolecules from the ionized analyte molecules.
 13. The method of claim10, further comprising: generating a potential gradient in a regionbetween the exit and the passageway into the mass spectrometer.
 14. Themethod of claim 13, wherein the directing of the ionized analytemolecules comprises attracting the molecules by action of the potentialgradient.
 15. An atmospheric pressure chemical ionization source for amass spectrometer comprising: means for vaporizing a fluid mixture ofmobile phase molecules and analyte molecules as the mixture travels toan exit having an axis; means for ionizing the vaporized analytemolecules using an electrical discharge arranged adjacent to the exit;and means for directing the ionized analyte molecules at an angle ofbetween about 75 and about 105 degrees with respect to the exit axistoward a passageway into the mass spectrometer.
 16. The atmosphericpressure chemical ionization source of claim 15, wherein the ionizedanalyte molecules are directed at an angle of about 90 degrees.
 17. Theatmospheric pressure chemical ionization source of claim 15, furthercomprising: means for desolvating mobile phase molecules from theionized analyte molecules.
 18. The atmospheric pressure chemicalionization source of claim 17, wherein the means for desolvatingincludes a drying gas.
 19. The atmospheric pressure chemical ionizationsource of claim 15, further comprising: means for generating a potentialgradient in a region between the exit and the passageway into the massspectrometer.
 20. An apparatus for providing ionized analyte moleculesto a mass analyzer comprising: a first passageway including an exithaving an axis, the first passageway providing a nebulized and ionizedaerosol including mobile phase molecules and analyte molecules anddischarging the aerosol through the exit, the exit being at a firstpotential; and an electrode maintained at a second potential, adifference between the second potential and the first potential of theexit causing ionized analyte molecules to be directed at an angle ofbetween about 75 and about 105 degrees with respect to the exit axisaway from the electrode and toward a second passageway into the massanalyzer.
 21. The apparatus of claim 20, wherein the ionized analytemolecules are directed at an angle of about 90 degrees.
 22. An apparatusfor providing ionized analyte molecules to a mass analyzer comprising: afirst passageway including an exit having an axis, the first passagewayproviding an aerosol including mobile phase molecules and analytemolecules and discharging the aerosol through the exit, the exit beingmaintained at a first potential; and an annular electrode arranged inthe vicinity of the exit of the first passageway and maintained at asecond potential, the potential difference between the second potentialand the first potential causing ionization of the analyte molecules inthe aerosol as they pass through the exit of the first passageway;wherein the ionized analyte molecules are thereafter directed at anangle of between about 75 and about 105 degrees with respect to the exitaxis toward a second passageway into the mass analyzer.
 23. Theapparatus of claim 22, wherein the analyte molecules are directed at anangle of about 90 degrees.
 24. An apparatus for providing ionizedanalyte molecules to a mass spectrometer, comprising: means fornebulizing a fluid mixture of mobile phase molecules and analytemolecules into an aerosol; means for ionizing the analyte and mobilephase molecules in the aerosol; exit means for spraying the aerosolalong an axis, the exit means being at a first potential; means forgenerating a second potential different from the first potential, thepotential difference between the first and second potentials directingthe ionized analyte molecules in the aerosol at an angle of betweenabout 75 and about 105 degrees with respect to the axis toward apassageway into the mass spectrometer.
 25. The apparatus of claim 24,wherein the potential difference directs the ionized analyte moleculesat an angle of about 90 degrees.
 26. The apparatus of claim 24, furthercomprising: means for desolvating mobile phase molecules from theionized analyte molecules.